Changes in specific IgE and IgG and monocyte chemoattractant protein-1 in workers with occupational asthma caused by diisocyanates and removed from exposure.
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Asthma↗
Biomedical subjects
David Bernstein
Publications and source records attributed to David Bernstein.
Effect of asthma on the risk of obstructive sleep apnea syndrome in atopic women.
BACKGROUND: Obstructive sleep apnea syndrome is associated with significant morbidity and remains underdiagnosed in women. Identification of high-risk groups among women is important for early detection and treatment. OBJECTIVE: To describe the prevalence of snoring in young women with atopy and to determine the risk factors for snoring in these individuals. METHODS: The Cincinnati Childhood Allergy and Air Pollution Study is an ongoing prospective birth cohort study of infants with at least 1 atopic parent. Mothers of study participants were evaluated by questionnaire for snoring, respiratory symptoms, and smoking status. Women who snored were compared with those who did not snore. Logistic regression analysis was performed to determine risk factors for snoring. RESULTS: Data were available on 677 women who had at least 1 live birth. Of these 677 women, 546 (81%) were white, 122 (18%) were African American, and 9 (1%) were biracial or Asian. The mean +/- SD age of the cohort at the time of evaluation for snoring was 29.6 +/- 5.6 years. Of the 677 women, 231 (34%) reported snoring at least 1 night per week, and snoring almost always (5-7 nights per week) was reported by 85 (13%). An almost 2-fold risk of snoring was associated with asthma (diagnosis and current symptoms) (odds ratio, 1.8; 95% confidence interval, 1.1-2.8) and African American race (odds ratio, 1.6; 95% confidence interval, 1.04-2.6) after controlling for income level and smoking status. CONCLUSIONS: We found a high prevalence of snoring inyoung women with atopy and a significant association with asthma.
Adult↗
Mold damage in homes and wheezing in infants.
BACKGROUND: In most studies that investigate the association of mold or water damage and respiratory disorders in infants, the analysis is not adjusted for exposure to house dust mite (HDM), which is also a known cause of respiratory illnesses. OBJECTIVE: To investigate the relationship between visually observable mold or water damage and HDM (Der f 1) levels and the prevalence of lower respiratory tract symptoms and allergen sensitization in infants of atopic parents as part of a prospective birth cohort study. METHODS: On-site home visits (at the infants' age of 8 months) were performed to evaluate observable mold or water damage and HDM exposure. At a clinic visit near the infant's first birthday, medical histories, including parent-reported wheezing episodes, and a skin prick test to food and 15 common aeroallergens were conducted in 640 infants. RESULTS: More than half of the homes were found to have mold or water damage, and 5% had major mold or water damage with visible mold at 0.2 m2 or more. Only 16% of homes had a HDM allergen (Der f 1) concentration of more than 2 microg/g. Major mold or water damage increased the risk of recurrent wheezing nearly 2 times in infants, 5 times in food or aeroallergen-sensitized infants, and 6 times in aeroallergen-sensitized infants. Neither visible mold or water damage nor HDM exposure was associated with sensitization to either mold or aeroallergens. CONCLUSIONS: Visible mold was shown to be a significant risk factor for recurrent wheezing in infants at high risk of developing atopic disorders, whereas HDM exposure did not significantly increase the risk.
Allergens↗
Atopy as a risk factor for habitual snoring at age 1 year.
STUDY OBJECTIVES: To determine the prevalence of habitual snoring (HS) in 1-year-old children, and to assess the relationship between HS and atopic status in these children. DESIGN: Cross-sectional evaluation of a birth cohort selected from the population. SETTING: Ohio and Kentucky River Valley communities. PARTICIPANTS: Children participating in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) were recruited for this study. MEASUREMENTS AND RESULTS: At age 1 year, the children were evaluated for atopic status and exposure to environmental tobacco smoke (ETS). Parents were asked to complete a questionnaire pertaining to their snoring frequency and that of their child. Children with HS (snoring three or more times per week) were compared to those who either did not snore or snored less than three times per week. Data were available on 681 of the 700 children participating in CCAAPS study. Of these 681 children (377 boys and 304 girls), 542 were white (80%), 118 were African American (17%), and 21 were biracial or Asian (3%). The mean age (+/- SD) of our cohort at the time of assessment for snoring was 13.7 +/- 2.6 months. Of the 681 children, 105 snored habitually (15%). There was a significant association between HS and the following: (1) positive atopic status (p = 0.005); (2) African-American race (p < 0.01); and (3) a history of snoring in the father (p < 0.01) or in the mother (p < 0.01). There was, however, no association between HS and ETS. CONCLUSIONS: We found a 15% prevalence of HS in 1-year-old children born to atopic parents and a significant association with positive atopic status.
Cohort Studies↗
Simulating mesoscopic reaction-diffusion systems using the Gillespie algorithm.
We examine an application of the Gillespie algorithm to simulating spatially inhomogeneous reaction-diffusion systems in mesoscopic volumes such as cells and microchambers. The method involves discretizing the chamber into elements and modeling the diffusion of chemical species by the movement of molecules between neighboring elements. These transitions are expressed in the form of a set of reactions which are added to the chemical system. The derivation of the rates of these diffusion reactions is by comparison with a finite volume discretization of the heat equation on an unevenly spaced grid. The diffusion coefficient of each species is allowed to be inhomogeneous in space, including discontinuities. The resulting system is solved by the Gillespie algorithm using the fast direct method. We show that in an appropriate limit the method reproduces exact solutions of the heat equation for a purely diffusive system and the nonlinear reaction-rate equation describing the cubic autocatalytic reaction.
Journal Article↗
Pegylated interferon alpha-2a with or without ribavirin in HCV/HIV coinfection: partially blinded, randomized multicenter trial.
We evaluated the safety and efficacy of peginterferon alpha-2a (pegIFNalpha-2a), with or without ribavirin, in 154 HCV/HIV coinfected patients. All received pegIFNalpha-2a (180 microg/week) for 12 weeks, with those achieving an early virologic response (EVR) continued on monotherapy through week 48. Patients without an EVR were randomized at week 14 to also receive ribavirin (800 mg/day) or placebo through week 48. Patients with detectable HCV RNA at week 24 were discontinued. An EVR occurred in 59 of 154 patients on monotherapy, and a sustained virologic response (SVR) occurred in 19 of 55 of those achieving an EVR and continuing monotherapy through week 48. One week 12 nonresponder receiving pegIFNalpha-2a plus ribavirin, and none receiving pegIFNalpha-2a plus placebo, achieved a SVR. Discontinuations for adverse events occurred in 10 of 154 patients before, and 16 of 131 after, week 14. HIV RNA and CD4 counts did not change significantly during treatment. PegIFNalpha-2a was therefore at least as effective as standard interferon and ribavirin combination therapy and was well tolerated, without a negative impact on HIV parameters.
Adult↗
Is it traffic type, volume, or distance? Wheezing in infants living near truck and bus traffic.
BACKGROUND: Previous studies of air pollution have not examined the association between exposure to varying types, distance, and amounts of traffic and wheezing in very young infants. OBJECTIVE: We sought to determine the relationship between types of traffic, traffic volume, and distance and wheezing among infants less than 1 year of age. METHODS: A geographic information system and a classification scheme were developed to categorize infants enrolled in the study as living near moving truck and bus traffic (highway >50 miles per hour, >1000 trucks daily, <400 m), stop-and-go truck and bus traffic (<50 miles per hour, <100 m), or unexposed and not residing near either. Symptom data were based on health questionnaires administered to parents when the infants were 6 months of age and monthly health diaries. RESULTS: Infants living very near (<100 m) stop-and-go bus and truck traffic had a significantly increased prevalence of wheezing (adjusted odds ratio, 2.50; 95% CI, 1.15-5.42) when compared with unexposed infants. The prevalence of wheezing among nonwhite infants was at least twice that of white infants, regardless of exposure. Infants living less than 400 m from a high volume of moving traffic, however, did not have an increased prevalence of wheezing. CONCLUSION: These results suggest that the distance from and type of traffic exposures are more significant risk factors than traffic volume for wheezing in early infancy.
Environmental Exposure↗
The biopersistence of Canadian chrysotile asbestos following inhalation: final results through 1 year after cessation of exposure.
Chrysotile asbestos, a serpentine mineral, has been shown to be notably different from amphibole asbestos such as amosite, crocidolite, and tremolite in that chrysotile once inhaled is rapidly removed from the lung while the amphiboles persist. This has been demonstrated for three different chrysotile samples from Canada, the United States, and Brazil. The initial results of the inhalation biopersistence study on the Canadian chrysotile were reported earlier. This article presents the full results through 365 days after cessation of exposure. In order to fully understand the dynamics of the clearance of chrysotile from the lung, the study included a standardised inhalation biopersistence study following the recommendations of the European Commission (EC) Interim Protocol for the Inhalation Biopersistence of synthetic mineral fibers (Bernstein & Riego-Sintes, 1999) in which the lungs were digested to evaluate fiber content remaining. In addition, confocal microscopy was used to examine lungs in three dimensions to determine where and what size the remaining fibers were in the lung tissue. The results showed that Canadian chrysotile is cleared from the lung with a clearance half-time of 11.4 days for the fibers longer than 20 microm. Canadian chrysotile clears in a range similar to that of glass and stone wools. It remains less biopersistent than ceramic and special purpose glasses and considerably less biopersistent than amphibole asbestos. At 1 yr after cessation of exposure, no long (L>20 microm) chrysotile fibers remained in the lung. In contrast, with amosite asbestos there were 4 x 10 (5) long fibers (L>20 microm) remaining in the lungs at one year after cessation of exposure (Hesterberg et al., 1998). These results fully support the differentiation of chrysotile from amphiboles reported in recent evaluations of available epidemiological studies (Hodgson & Darnton, 2000; Berman & Crump, 2004).
Animals↗
Testing of fibrous particles: short-term assays and strategies.
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Air Pollutants↗
Binding specificity and mRNA targets of a C. elegans PUF protein, FBF-1.
Sequence-specific RNA-protein interactions underlie regulation of many mRNAs. Here we analyze the RNA sequence specificity of Caenorhabditis elegans FBF-1, a founding member of the PUF protein family. Like other PUF proteins, FBF-1 binds to the 3' UTR of target mRNAs and decreases expression of those target genes. Here, we show that FBF-1 and its close relative, FBF-2, bind with similar affinity to multiple RNA sites. We use mutagenesis and in vivo selection experiments to identify nucleotides that are essential for FBF-1 binding. The binding elements comprise a "core" central region and flanking sequences. The core region is similar but distinct from the binding sites of other PUF proteins. We combine the identification of binding elements with informatics to predict new FBF-1 binding sites in a C. elegans 3' UTR database. These data identify a set of new candidate mRNA targets of FBF-1 and FBF-2.
Amino Acid Sequence↗
Glycoprotein D adjuvant herpes simplex virus vaccine.
Herpes simplex virus (HSV) Type-1 and -2 are common infections that can cause primary and recurrent herpes labialis and genitalis, as well as gingivostomatitis, keratoconjunctivitis, encephalitis, disseminated infections in immunocompromised persons and neonatal infections. Despite several decades of HSV vaccine development, no effective vaccine has been developed until recently. The following review of the genital HSV-2 glycoprotein D (gD2t, t is for truncated) subunit vaccine formulated with a new adjuvant (AS04) containing alum and 3-O deacylated monophosphoryl lipid A (MPL) provides a background in which to evaluate the vaccine as well as a brief review of other approaches to herpes vaccines. The gD2t-AS04 vaccine has been demonstrated to be safe in several large clinical trials. In two trials, the vaccine reduced genital herpes disease by 73 and 74%, but only in females with no previous HSV infection. A large ongoing trial in HSV seronegative females will provide additional data on protection from HSV disease and infection.
Adjuvants, Immunologic↗
RNA-protein interactions in the yeast three-hybrid system: affinity, sensitivity, and enhanced library screening.
The yeast three-hybrid system has become a useful tool in analyzing RNA-protein interactions. An RNA sequence is tested in combination with an RNA-binding protein linked to a transcription activation domain (AD). A productive RNA-protein interaction activates a reporter gene in vivo. The system has been used to test candidate RNA-protein pairs, to isolate mutations in each interacting partner, and to identify proteins that bind a given RNA sequence. However, the relationship between reporter gene activation and in vitro affinity of an RNA-protein interaction has not been examined systematically. This limits interpretation of the data and complicates the development of new strategies. Here, we analyze several key parameters of the three-hybrid system, using as a model the interaction of a PUF protein, FBF-1, with a range of RNA targets. We compare activation of two reporter genes as a function of the in vitro affinity of the interaction. HIS3 and LacZ expression levels are directly related to affinity over a 10-fold range of Kd. Expression of the reporter genes also is directly related to the abundance of the activation domain fusion protein. We describe a new yeast strain, YBZ1, that simplifies screening of cDNA/AD libraries. This strain possesses a tandem, head-to-tail dimer of a high-affinity variant of MS2 coat protein, fused to a monomer of the LexA DNA-binding protein. We show that the use of this strain in cDNA library screens increases the number of genuine, sequence-specific positives detected, and at the same time reduces the background of false, RNA-independent positives.
Adaptor Proteins, Signal Transducing↗
Prevalence of antibody to Bordetella pertussis antigens in serum specimens obtained from 1793 adolescents and adults.
Serum specimens were obtained from all subjects in the adolescent and adult acellular pertussis (aP) vaccine efficacy trial before and after immunization to study the prevalence of IgG and IgA antibody and geometric mean titers to 4 Bordetella pertussis antigens. Of 1793 adolescents and adult subjects who received aP vaccine, only 20%, 68%, 59%, and 39% had concentrations of IgG antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3, respectively, that were greater than or equal to the limit of quantitation of the enzyme-linked immunosorbent assay used in the analysis. There was minimal variation in antibody prevalence with respect to geographic area, age, sex, or race.
Adolescent↗
Immune responses and antibody decay after immunization of adolescents and adults with an acellular pertussis vaccine: the APERT Study.
As part of a prospective acellular pertussis (ACP) vaccine efficacy trial, 5 serum samples were obtained, over an 18-month period, from 101 ACP-vaccine recipients and 99 control subjects, to assess ACP antibody response and decay. Immunoglobulin (Ig) G and IgA antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae 2/3 (FIM) were measured by enzyme-linked immunosorbant assay, and titers of agglutinin were determined. Of the subjects, 16%-19% had preimmunization values of antibodies to PT that were above the assay's limit of quantitation (LOQ); in contrast, 36%-63% of the subjects had preimmunization values of antibodies to FHA, PRN, or FIM that were above the LOQ. Substantial increases in titers of IgG and IgA antibodies to the 3 ACP antigens (PT, FHA, and PRN) were observed. Over the 18-months, the percent decay in IgG and IgA antibodies ranged from 56% to 73% and from 57% to 70%, respectively; the IgG antibody response and decay suggests that geometric mean titers likely remain above the LOQ for 2-9 years and above the threshold of detection for 4-13 years. These findings support the use of ACP booster immunizations for adolescents and adults, to provide sustained levels of antibody.
Adolescent↗
Quantitative PCR analysis of house dust can reveal abnormal mold conditions.
Indoor mold concentrations were measured in the dust of moldy homes (MH) and reference homes (RH) by quantitative PCR (QPCR) assays for 82 species or related groups of species (assay groups). About 70% of the species and groups were never or only rarely detected. The ratios (MH geometric mean : RH geometric mean) for 6 commonly detected species (Aspergillus ochraceus, A. penicillioides, A. unguis, A. versicolor, Eurotium group, and Cladosporium sphaerospermum) were >1 (Group I). Logistic regression analysis of the sum of the logs of the concentrations of Group I species resulted in a 95% probability for separating MH from RH. These results suggest that it may be possible to evaluate whether a home has an abnormal mold condition by quantifying a limited number of mold species in a dust sample. Also, four common species of Aspergillus were quantified by standard culturing procedures and their concentrations compared to QPCR results. Culturing underestimated the concentrations of these four species by 2 to 3 orders of magnitude compared to QPCR.
Air Pollution, Indoor↗
Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.
BACKGROUND: Treatment with pegylated interferon (peginterferon) and ribavirin for 48 weeks is more effective than conventional interferon and ribavirin in patients with chronic hepatitis C. OBJECTIVE: To assess the efficacy and safety of 24 or 48 weeks of treatment with peginterferon-alpha2a plus a low or standard dose of ribavirin. DESIGN: Randomized, double-blind trial. SETTING: 99 international centers. PATIENTS: 1311 patients with chronic hepatitis C. INTERVENTION: Peginterferon-alpha2a, 180 microg/wk, for 24 or 48 weeks plus a low-dose (800 mg/d) or standard weight-based dose (1000 or 1200 mg/d) of ribavirin. MEASUREMENT: Sustained virologic response: undetectable HCV RNA concentration at the end of treatment and during 12 to 24 weeks of follow-up. RESULTS: Overall and in patients infected with HCV genotype 1, 48 weeks of treatment was statistically superior to 24 weeks and standard-dose ribavirin was statistically superior to low-dose ribavirin. In patients with HCV genotype 1, absolute differences in sustained virologic response rates between 48 and 24 weeks of treatment were 11.2% (95% CI, 3.6% to 18.9%) and 11.9% (CI, 4.7% to 18.9%), respectively, between standard- and low-dose ribavirin. Sustained virologic response rates for peginterferon-alpha2a and standard-dose ribavirin for 48 weeks were 63% (CI, 59% to 68%) overall and 52% (CI, 46% to 58%) in patients with HCV genotype 1. In patients with HCV genotypes 2 or 3, the sustained virologic response rates in the 4 treatment groups were not statistically significantly different. CONCLUSION: Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype. Patients with HCV genotype 1 require treatment for 48 weeks and a standard dose of ribavirin; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks.
Adult↗
Treatment of chronic hepatitis C in a state correctional facility.
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Data Interpretation, Statistical↗
FBF-1 and FBF-2 regulate the size of the mitotic region in the C. elegans germline.
In the C. elegans germline, GLP-1/Notch signaling and two nearly identical RNA binding proteins, FBF-1 and FBF-2, promote proliferation. Here, we show that the fbf-1 and fbf-2 genes are largely redundant for promoting mitosis but that they have opposite roles in fine-tuning the size of the mitotic region. The mitotic region is smaller than normal in fbf-1 mutants but larger than normal in fbf-2 mutants. Consistent with gene-specific roles, fbf-2 expression is limited to the distal germline, while fbf-1 expression is broader. The fbf-2 gene, but apparently not fbf-1, is controlled by GLP-1/Notch signaling, and the abundance of FBF-1 and FBF-2 proteins is limited by reciprocal 3'UTR repression. We propose that the divergent fbf genes and their regulatory subnetwork enable a precise control over size of the mitotic region. Therefore, fbf-1 and fbf-2 provide a paradigm for how recently duplicated genes can diverge to fine-tune patterning during animal development.
3' Untranslated Regions↗